The acute and chronic effects of antipsychotic drugs (APD) will be investigated in several brain regions of the rat. It is hypothesized that APD block dopamine (DA) receptors in the frontal cortex (FC) and that these receptors have properties different from their counterparts in the caudate nucleus (CN) or olfactory tubercles (OT). These hypotheses are investigated by in vivo and in vitro biochemical methods, specifically computer-assisted gas-chromatography-mass-spectrometry, radioenzymatic assays, and in vitro binding assays. These parameters and their interaction with APD, administered acutely or chronically, are investigated in control animals and in animals with lesions of the dopaminergic or serotonergic pathways to the cortex. The significance of these pathways in the in vivo effects of APD can thus be ascertained. Comparisons between biochemical and behavioral alterations during chronic treatment with APD may offer insights into the mechanisms underlying the development of tolerance to some of the effects of APD.